Sickle cell disease and nitrous oxide-induced neuropathy

Abstract

We report three cases of peripheral neuropathy in patients with sickle cell disease. All had a history of frequent painful crises and regular attendance at our Accident and Emergency department where nitrous oxide analgesia was administered for prolonged periods. All three patients (one male and two females) presented with difficulty in walking associated with paraesthesiae, and neurological examination revealed signs compatible with a peripheral sensorimotor neuropathy, later confirmed by nerve conduction studies. Serum vitamin B12 levels were mildly reduced in two patients and very low in one patient (< 10 ng/l). Haemoglobin levels in all the patients were unchanged compared with their steady-state levels but one had developed a macrocytosis (103 fl). Schilling tests were normal in two patients, and two patients had negative gastric parietal antibodies. All three patients were given intramuscular vitamin B12 in addition to avoiding further exposure to nitrous oxide, and their neurological symptoms improved completely. As nitrous oxide is known to cause a neuropathy similar to that seen in pernicious anaemia, we postulate that nitrous oxide analgesia combined with low B12 levels was the cause of the marked neuropathy in these patients. As a result of our observations and the probable association, we now do not use nitrous oxide analgesia in the management of patients with sickle cell disease.

Guidelines for the management of the acute painful crisis in sickle cell disease

“…Analgesia should be started within 30 min of arrival in hospital after a rapid initial assessment and the pain should be controlled within 60 min of starting analgesia. Nitrous oxide (50%) and oxygen (50%) (Entonox, Equanox) can be used in the ambulance and for the first 30–60 min in hospital, but should not be continued long‐term because of the risk of megaloblastic anaemia and neuropathy (Ogundipe et al , 1999). Individual patients may find it particularly useful and its short‐term use can be included in personalized care plans.…”

Peripheral neuropathy following nitrous oxide abuse

“…It is recognized as being safe and a useful pain‐relieving adjuvant during many varied procedures performed in the ED. The main risks of use are associated with maintaining an adequate oxygen mix, suspected pneumothorax, and care when using with individuals with depleted B12 stores or sickle cell disease 1,2 where it has resulted in the development of transient neurological symptoms. Some of the earliest case reports noting an association between N2O abuse and developing neurological symptoms was in health‐care workers 3,4 …”

Resolution of Acute Priapism in Two Children With Sickle Cell Disease Who Received Nitrous Oxide

“…Nitrous oxide has few side effects and rare serious adverse effects when used infrequently; however, recurrent N 2 O use or abuse can cause neurologic complications through impact on vitamin B12 (cobalamin) metabolism . Ogundipe et al . reported three cases of peripheral neuropathy in young adults with SCD who had frequent, prolonged N 2 O exposure.…”